The overall aim of this research project is to precisely characterize the nature and sequence of metabolic change during the onset of ischemia and anoxia. We hypothesize that the accumulation of such metabolites as long-chain acyl CoA (LCACAE) and long-chain acyl carnitine esters during ischemia or anoxia may cause inhibition of a number of key mitochondrial-linked enzyme systems. We hope to establish that the ratio of LCACAE to carnitine, by virtue of its effect upon mitochondrial enzymes, may regulate myocardial respiration and play a critical role in the recovery of the myocardium from ischemia. The properties of the enzyme, carnitine acetyl transferase, and its function in the normal and ischemic myocardium will also be studied. Efforts will be made to determine the role of acetyl carnitine formation during ischemia. These studies are part of a broader investigation aimed at determining the mechanism by which carnitine protects the ischemic myocardium.